Seizure 29 (2015) 20–25
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Latency of interictal epileptiform discharges in long-term EEG recordings in epilepsy patients Konrad J. Werhahn a,1,*, Elisabeth Hartl b,1, Kristin Hamann a, Markus Breimhorst a, Soheyl Noachtar b a b
Department of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Germany Epilepsy Center, Department of Neurology, University of Munich, Germany
A R T I C L E I N F O
A B S T R A C T
Article history: Received 24 December 2014 Received in revised form 4 February 2015 Accepted 17 March 2015
Purpose: To assess the latency of interictal epileptiform discharges (IED) and seizures in long-term EEG recordings of patients with epilepsy. Method: IED latency was measured in 210 consecutive patients (mean (SD) age 38.6 13.9 years) with active epilepsy and the relationship to clinical variables was analyzed retrospectively. Median duration of EEG recording was 101.5 h (95% confidence interval [CI] 92 to 117 h). Results: IEDs were absent in 45 (21.4%) and present in 165 (78.6%) patients who had a longer duration (p < 0.001) and early onset (p < 0.01) of epilepsy and more often had IEDs in prior standard EEGs (p < 0.01), a structural etiology (OR 2.4, CI: 2.1–2.7), or temporal lobe epilepsy (OR 9.6, CI: 9.0–10.2). IED latency did not correlate with other clinical variables. Median latency to the emergence of the first IED was 9.3 h (CI: 7.5–11.4) occurring in 7.3%, 9.7%, 74.6%, 87.9%, and 96.4% within 20 min, 30 min, 24 h, 48 h, and 72 h, respectively. Seizure frequency was higher in patients with (n = 165) than without IEDs (n = 45) (72.1% vs. 46.6%, p < 0.01) and seizure latency (median 21.6 h, CI: 16.8–27.3) was influenced by the presence of IEDs, whereas the presence of seizures did not influence the latency and frequency of IEDs. Conclusion: If present, in the majority of epilepsy patients IEDs occurred during the first 72 h of longterm video-EEG recording. Repeated video-EEG or video recordings of habitual seizures are needed to minimize false negative studies. ß 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Keywords: Epilepsy Interictal epileptiform discharges Long-term EEG Latency
1. Introduction In EEG, particular sharp transients like spikes, sharp waves, spike-wave complexes or polyspikes are summarized as interictal epileptiform discharges (IEDs) [1,2]. They are characteristic for patients with epilepsy and reflect a hyperexcitability and functional impairment of the brain. The EEG-recording of IEDs can be helpful to establish the diagnosis of epilepsy in patients with paroxysmal events but unreliable history or lack of seizure description [3–5]. However, the sensitivity of routine EEGs is low. After the first or second seizure, standard EEG reveals IEDs in only
* Corresponding author at: Alfred-Nobel Str. 10, D-40789 Monheim, Germany. Tel.: +49 2173 48 1486; fax: +49 2173 48 1331. E-mail addresses:
[email protected] (K.J. Werhahn),
[email protected] (E. Hartl),
[email protected] (K. Hamann),
[email protected] (M. Breimhorst),
[email protected] (S. Noachtar). 1 Co-first author.
12.5–50% of the epilepsy patients [6,7]. Thus, an epileptic seizure etiology cannot be eliminated immediately after a single normal EEG recording. In epilepsy patients IED frequency varies interindividually and is associated with some clinical factors, like duration of epilepsy [8,9] or time to last seizure [10–15], others, like seizure frequency or antiepileptic drug use, are controversial [8–11,14,16]. The IED yield can be increased up to 92% by multiple repetition of the EEG recording [6], implementation of activation methods and EEG performance during sleep or after sleep deprivation [6,7,10,12,17– 21]. Alternatively, EEG recordings can be done over a longer period of time. Only in few epilepsy patients no IEDs can be found, e.g. in patients with grand-mal or frontal lobe epilepsy [21]. In healthy subjects, though, IEDs only occur in 0.5–2% [22,23]. Thus it is of interest how long EEG recordings have to be done to detect IEDs, if present, with reasonable certainty and to identify those patients without IEDs. While there is evidence suggesting that a three day telemetry EEG is sufficient to detect seizures in the majority of patients, the latency of IEDs in long-term EEG has only been
http://dx.doi.org/10.1016/j.seizure.2015.03.012 1059-1311/ß 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
K.J. Werhahn et al. / Seizure 29 (2015) 20–25
studied either with a limited number of patients or with short EEG recordings [24–27]. Inpatient long-term EEG is expensive in terms of personnel and technical resources. Costs for EEG monitoring (without video) for inpatients has been estimated to be $900–$1400 per day in the US, s567 per day in Europe (mean of n = 10, personal communication of own data) and around $70 per day in India [28,29]. In addition to the use of limited hospital beds, the EEG analysis requires the involvement of a highly specialized team. Therefore, knowledge about the probability to detect an IED in long-term EEG recordings within a given time impacts clinically to make a firm diagnosis and economically to estimate the time of recording. The purpose of our study was to determine the latency of IEDs in long-term EEGs in patients with epilepsy, the relation between IED and seizure latency, and the clinical parameters affecting IED latency. 2. Material and methods This study complies with the institutional review boardapproved ethical guidelines of the University of Mainz and all patients had given written informed consent to the scientific use of their clinically acquired, anonymized data. 2.1. Participants We performed a retrospective analysis of 300 consecutive patients admitted to the video-EEG lab at the University of Mainz, Epilepsy Center (Germany). Patients were referred for syndrome classification, evaluation for surgery, or differential diagnostic allocation of unclear paroxysmal events. We documented demographics as well as seizure type, epilepsy syndrome, etiology of epilepsy, age of onset, duration of epilepsy, current number of antiepileptic drugs (AEDs) at the beginning of EEG recordings, EEG results, imaging findings, and seizure frequency at the time of admission and in the previous 12 months. In patients on antiepileptic treatment at the time of admission, AEDs were reduced using the following general principles: (1) if prior intake >1 AED: stop all but one AEDs, but leave one AED on full dose on the first day and reduce to basic dose (approx. 50–75% of lowest indicated dose) on days 2–5; (2) if only one baseline AED reduce to basic dose (as above) on day 1; (3) give lorazepam 2.5 mg sublingual after each generalized tonic-clonic seizure. Patients with unclear paroxysmal events (n = 90) and no evidence of epilepsy by history and from previous long-term EEGs were excluded. Therefore, only patients with unequivocal epilepsy (n = 210) based on witnessed seizure reports and/or interictal or ictal epileptiform discharges on EEG were analyzed for this report. Epilepsy syndromes were classified (by KJW) using a semiological seizure classification [30] and including all available clinical information. Continuous video-EEG recordings were done over a median of 101.5 h [range 3–399, mean SD = 120.7 62.7, 90% 60 h] using 24- (n = 26) or 32- (n = 184) channel surface EEG with gold cup electrodes (Grass Technologies, West Warwick, RI) attached to the skull (10/20 and 10/10 positions) using collodion. EEGs were sampled at 512 Hz, filtered [0.1–70 Hz] and reviewed [usually 15 mV/mm, 30 mm/s] on a 300 PC Monitor using a conventional EEG software (Excel-Tech Ltd., Toronto, Canada). EEG recordings usually started during the late morning to early afternoon (median time of start of the recording 12:44 pm). Anonymized EEGs were independently analyzed by two experienced board-certified EEG readers (one epileptologist and one neurologist). Both EEG readers independently had to agree upon the first interictal epileptiform discharge (IED) from the onset of EEG recording. In case of disagreement, EEG traces were reviewed with both readers present and a consensus was reached on a
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case by case basis or the IED discarded in case of disagreement. From the beginning of the recording, all EEG records were manually screened at least until the first IED was noted. All first IEDs and their latency were marked and the state of vigilance (awake or sleep) recorded. An IED was defined as a spike, spike- or sharp-wave or polyspike of
